Prognostic significance of omental disease and the role of omentectomy in non-endometrioid endometrial cancer.

OBJECTIVES: Non-endometrioid endometrial cancers (non-EEC) have different management from endometrioid endometrial cancers. The purpose of this study was to investigate the prognostic significance of omental disease and the role of omentectomy in non-endometrioid endometrial cancer and discuss the current literature with the findings. MATERIAL AND METHODS: The study included two hundred-three patients with non-EEC who underwent surgical treatment and follow-up between January 1996 and December 2018 in a University Hospital Gynecologic Oncology Center. The patients were divided into three groups according to whether omentectomy was performed and the presence of omental metastasis. The patient's demographics, clinical characteristics such as stage, grade, histopathologic type, lymphovascular space invasion (LVSI), myometrial invasion, lymph node involvement, and survival outcomes were compared between the groups. RESULTS: The study included 203 patients. Twenty-five patients (12%) had omental metastases. LVSI was reported in 57.3%, 88.0%, and 43.2% of the non-omentectomy, no-omental metastasis, and omental metastatic groups, respectively (p = 0.001). The 5-year disease-free survival (DFS) and overall survival (OS) rates according to the tumor grade, peritoneal cytology, and lymphadenectomy were also compared and were found to be statistically similar. The five-year OS rates were 70.6% for the group without omental metastases and 16.2% for the group with omental metastases, respectively (p = 0.001). In the group of omentectomy, the five-year DFS rates were 62.2% in cases without omental metastasis and 13.0% in cases with omental metastasis (p = 0.001). The five-year OS rates of 86.3% and DFS rates of 80.0% in the group without omentectomy. CONCLUSIONS: In non-endometrioid tumors, the survival rate was better in the group that did not undergo omentectomy. Based on these results, we can say that omentectomy may not be necessary for non-endometrioid tumors whose omentum is found to be normal in intraoperative visual examination.

Survival outcomes of women with grade 3 endometrioid endometrial cancer: the impact of adjuvant treatment strategies.

AIM: This multicenter investigation was performed to evaluate the adjuvant treatment options, prognostic factors, and patterns of recurrence in patients with grade 3 endometrioid endometrial cancer (G3-EEC). MATERIALS AND METHODS: The medical reports of patients undergoing at least total hysterectomy and salpingo-oophorectomy for G3-EEC between 1996 and 2018 at 11 gynecological oncology centers were analyzed. Optimal surgery was defined as removal of all disease except for residual nodules with a maximum diameter ≤ 1 cm, as determined at completion of the primary operation. Adequate systematic lymphadenectomy was defined as the removal of at least 15 pelvic and at least 5 paraaortic LNs. RESULTS: The study population consists of 465 women with G3-EEC. The 5-year disease-free survival (DFS) and overall survival (OS) rates of the entire cohort are 50.3% and 57.6%, respectively. Adequate systematic lymphadenectomy was achieved in 429 (92.2%) patients. Optimal surgery was achieved in 135 (75.0%) patients in advanced stage. Inadequate lymphadenectomy (DFS; HR 3.4, 95% CI 3.0-5.6; P = 0.016-OS; HR 3.2, 95% CI 1.6-6.5; P = 0.019) was independent prognostic factors for 5-year DFS and OS. CONCLUSION: Inadequate lymphadenectomy and LVSI were independent prognostic factors for worse DFS and OS in women with stage I-II G3-EEC. Adequate lymphadenectomy and optimal surgery were independent prognostic factors for better DFS and OS in women with stage III-IV G3-EEC.

Discovery of metabolomic biomarkers for discriminating platinum-sensitive and platinum-resistant ovarian cancer by using GC-MS.

This study aims to determine ovarian cancer (OC) patients with platinum resistance for alternative treatment protocols by using metabolomic methodologies. Urine and serum samples of platinum-resistant and platinum-sensitive OC were analyzed using GC-MS. After data processing of GC-MS raw data, multivariate analyses were performed to interpret complex data for biologically meaningful information and to identify the biomarkers that cause differences between two groups. The biomarkers were verified after univariate, multivariate, and ROC analysis. Finally, metabolomic pathways related to group separations were specified. The results of biomarker analysis showed that 3,4-dihydroxyphenylacetic acid, 4-hydroxybutyric acid, L-threonine, D- mannose, and sorbitol metabolites were potential biomarkers in urine samples. In serum samples, L-arginine, linoleic acid, L-glutamine, and hypoxanthine were identified as important biomarkers. R2Y, Q2, AUC, sensitivity and specificity values of platinum-resistant and sensitive OC patients' urine and serum samples were 0.85, 0.545, 0.844, 91.30%, 81.08 and 0.570, 0.206, 0.743, 77.78%, 74.28%, respectively. In metabolic pathway analysis of urine samples, tyrosine metabolism and fructose and mannose metabolism were found to be statistically significant (p < 0.05) for the discrimination of the two groups. While 3,4-dihydroxyphenylacetic acid, L-tyrosine, and fumaric acid metabolites were effective in tyrosine metabolism. D-sorbitol and D-mannose metabolites were significantly important in fructose and mannose metabolism. However, seven metabolomic pathways were significant (p < 0.05) in serum samples. In terms of p-value, L-glutamine in the nitrogen metabolic pathway from the first three pathways; L-glutamine and pyroglutamic acid metabolites in D-glutamine and D-glutamate metabolism. In the arginine and proline metabolic pathway, L-arginine, L-proline, and L-ornithine metabolites differed significantly between the two groups.

Feasibility and rationale of a novel approach in advanced ovarian cancer surgery: Bat- shaped en-bloc total peritonectomy and total hysterectomy salpingo-oophorectomy with or without rectosigmoid resection (Sarta-Bat approach).

OBJECTIVE: To evaluate the feasibility of bat-shaped en-bloc total peritonectomy and total hysterectomy-salpingo-oophorectomy with or without rectosigmoid resection as a novel approach in advanced ovarian cancer surgery. METHODS: Advanced ovarian cancer patients with widespread peritoneal implants requiring total peritonectomy were the subject of the study. Thirteen cases were operated with Sarta-Bat approach between February 2019 and July 2020. Patients' clinical and surgical data were collected and statistically analyzed. RESULTS: Median age of the patients was 52 (40-65). Histopathology of the tumors were high-grade serous carcinoma in 12 (92.3%) and carcinosarcoma in one (7.7%) cases and all of them originated from the ovary. Eight (61.5%), two (15.4%) and three (23.1%) patients were stage 3c, 4a, and 4b, respectively. Upper abdomen was involved in all cases. Nine cases underwent primary cytoreductive and four cases interval cytoreductive surgery. Sarta-Bat approach was performed as en-bloc total peritonectomy, total hysterectomy bilateral salpingo-oophorectomy with rectosigmoid resection in three and without rectosigmoid resection in 10 cases. Final surgery resulted in complete cytoreduction (no macroscopic residual) in all cases, with acceptable grade 2-3 morbidity rates. CONCLUSION: Sarta-Bat approach is a feasible and convenient technique for cytoreductive surgery of advanced ovarian cancer with disseminated peritoneal metastases.

Prognosis Trend of Grade 2 Endometrioid Endometrial Carcinoma: Toward Grade 1 or 3?

Although the prognostic significance of grade in endometrial cancer is well known, grade 2 cases have not been evaluated separately in most of the previous studies. In this study, we aim to investigate whether the oncologic outcomes of grade 2 endometrioid endometrial carcinomas trend towards grade 1 or 3 tumors. Patients' records and pathological reports were reviewed retrospectively and eligible patients with endometrioid endometrial carcinoma were determined and distributed into 3 groups according to their 1988 International Federation of Gynecology and Obstetrics (FIGO) grade. Groups' characteristics and oncologic outcomes were compared. Differences between grades were tested with z-test and adjusted by Bonferroni method. Kaplan-Meier method was performed for the survival analysis. In total, 776 patients of endometrioid endometrial carcinoma were included in this study. Mean follow-up time was 52 ± 14 months. Patients' mean age was 56.3 ± 10.8 years. Even though grade 2 endometrioid endometrial carcinomas were different from both grade 1 and 3 in terms of the pathological features, survival analyses demonstrated that their oncologic outcomes trended towards grade 1. The grade was determined as an independent prognostic factor for overall survival (OS). The interobserver reproducibility will be improved among pathologists by combining FIGO grade 1 and 2 endometrioid endometrial carcinomas, while prognosis prediction is not likely to be affected.

Laparoscopic surgery for low, intermediate and high-risk endometrial cancer.

OBJECTIVE: The aim of the present study was to compare the long-term outcomes of the laparotomy (LT) and laparoscopic surgery and to evaluate the results according to low, intermediate, and high-risk groups of endometrial cancer (EC). METHODS: We identified 801 patients with EC and these patients were classified as group 1, who underwent LT (n=515); and group 2, who underwent laparoscopy (LS) (n=286). Patient's demographics, clinical characteristics such as stage, grade, histopathologic type, lymphovascular space invasion, myometrial invasion, lymph node involvement, and risk groups, peri- and post-operative outcomes, and survival outcomes were compared between the groups according to risk classification. Survival outcomes were assessed using Kaplan-Meier method. RESULTS: The demographic characteristics of both groups were similar except age. Shorter hospital stay and fewer complications were observed in group 2. The overall survival (OS) were similar in the low, low-intermediate, high-intermediate and high-risk groups (p=0.269, 0.476, 0.078, and 0.085; respectively) for LS compared to LT. The covariate analysis revealed that the death and recurrence risks were approximately twice higher in the LT group than in the LS group (odds ratio [OR]=1.9; 95% confidence interval [CI]=1.2-3.1 for OS; OR=2.0; 95% CI=1.2-3.3 for disease-free survival). CONCLUSION: The results of our study support the well-known positive aspects of LS as well as safe and effective use in cases of intermediate and high-risk EC.

A novel technique: Carbon dioxide gas-assisted total peritonectomy, diaphragm and intestinal meso stripping in open surgery for advanced ovarian cancer (Çukurova technique).

OBJECTIVE: Most of the ovarian cancers are diagnosed at advanced stages. As peritoneal carcinomatosis increases, especially when it extends to the diaphragm and intestinal mesos, probability of obtaining complete cytoreduction is reduced. Complete cytoreduction (residue zero: R0) is one of the main factors affecting survival [1-3]. Here we present a novel technique of stripping the peritoneal surfaces as a part of cytoreductive surgery in such cases. METHODS: A 55year-old woman diagnosed with peritoneal carcinomatosis was considered appropriate for primary cytoreduction after assessment of her thorax-abdominopelvic tomography, which revealed resectable intra-abdominal disease. Upon laparotomy, omental cake adherent to pelvis-filling mass, disseminated implants on the diaphragm, meso of the descending colon and small intestine were observed. The mass invaded the rectosigmoid colon, uterus, adnexa and the bladder resulting in frozen pelvis. Palpable retroperitoneal pelvic and para-aortic lymph nodes were detected. On the other side, stomach, anti-mesenteric surfaces and mesentery root of the small bowel were tumor-free. Hence, upon these perioperative and preoperative imaging findings, complete cytoreduction was thought to be achievable. Therefore, primary cytoreduction was performed. Total omentectomy, hysterectomy with bilateral salpingo-oophorectomy, rectosigmoid low anterior resection and retroperitoneal lymphadenectomy were performed. With the assistance of an injector needle connected to the insufflator tube (as in laparoscopic surgery), carbon dioxide gas was blown into the right retroperitoneal area and subsequently peritoneum was rapidly stripped up to the right diaphragm. The same procedure was then applied to the diaphragm and meso of the bowels, respectively. Owing to this technique, total stripping of all involved peritoneal surfaces was clearly facilitated and R0 goal was reached. RESULTS: Gas insufflation caused convenient detachment of the peritoneal surfaces along their anatomical line which led to concluding the stripping procedures easily, rapidly and safely without bleeding. Thus, according to our experience, about 10 to 15min per procedure are saved in such cases. Potential complications of CO2 gas used here are not superior to those in transperitoneal or retroperitoneal laparoscopic procedures. During the operation, patient was followed-up for potential complications such as subcutaneous emphysema and CO2 gas embolism.Thus, hourly blood gas was monitored. Another potential complication is injury of the vessels while inserting the needle which can be avoided by cautious inserting under the peritoneal surfaces superficially and using transillumination. In case such injuries happen, tamponing is a sufficient measure. In our serial, no perioperative complications belonging to this technique were encountered. However, long term outcomes such as precise time difference, difference in blood loss, complication rates, adhesions, morbidity associated with this technique and its impact on survival of the patients with advanced ovarian cancer have yet to be investigated. Therefore, a prospective study to validate this technique's long-term usefulness has been initiated in our clinic. CONCLUSION: We believe that this practical and effective technique will offer significant improvements in efforts to achieve complete cytoreduction.

Does preoperative neutrophil to lymphocyte or platelet to lymphocyte ratios have a role in predicting borderline ovarian tumors?

BACKGROUND: to investigate the value of using preoperative neutrophil to lymphocyte and platelet to lymphocyte levels in the patients of borderline ovarian tumors. METHODS: During the period between January 2002 and December 2015, the pathology reports and archival files of the Gynecologic Oncology Department of Çukurova University Medical Hospital and the Gynecologic Oncology Department of Dumlupinar University, Evliya Çelebi Education and Research Hospital were retrospectively reviewed, and 144 patients of borderline ovarian tumor (as the study group) and 123 patients of serous cystadenoma (as the control group) were determined for eligibility in this study. Data regarding age, menopausal status, preoperative ultrasound findings, ca125 and complete blood counts were reviewed. Neutrophil to lymphocyte and platelet to lymphocyte ratios were calculated and these parameters were statistically compared between the groups. RESULTS: There was a statistically significant difference between the groups according to neutrophil count, platelet count, neutrophil to lymphocyte ratio and platelet to lymphocyte ratio; in addition to age, ca125 and preoperative ultrasound findings. CONCLUSIONS: It seems that neutrophil to lymphocyte and platelet to lymphocyte ratios are useful in predicting borderline ovarian tumors, preoperatively. However, further prospective studies are needed.

Fetal Oropharyngeal and Neck Tumors: Determination of the Need for Ex-Utero Intrapartum Treatment Procedure.

BACKGROUND: The aim of this study was to assess the ex-utero intrapartum therapy (EXIT) applied to 3 of the 7 cases with oropharyngeal or neck masses and review the indicators of the need for an EXIT procedure. CASE REPORT: Prenatal presentation, size and localization of the masses, existence of fetal hydrops and associated findings such as polyhydramnios, intraoperative managements, complications, and maternal and neonatal outcomes were evaluated through a retrospective analysis. Four cases had neck masses and three cases had oropharyngeal masses. Prenatal sonography was used as the main diagnostic tool for all patients. The median gestational age was 34.5 weeks at the time of diagnosis and 36 weeks at delivery. Polyhydramnios was observed in three of the seven cases and they were delivered prematurely. Interventions such as endotracheal intubation or tracheostomy were performed to provide patency of the airway during delivery by the EXIT procedure in three cases. Hemangioma was found in two cases, teratoma in two cases, lymphangioma in two cases and hamartoma in one case following pathological examination of the masses. CONCLUSION: The localization of mass, its characteristics, invasion (if it exists), and relation to the airway are the main factors used to determine the need for EXIT. The presence of polyhydramnios may be an important indicator to predict both the need for EXIT and fetal outcomes.

Evaluation of endometrial thickness and bone mineral density based on CYP2D6 polymorphisms in Turkish breast cancer patients receiving tamoxifen treatment.

BACKGROUND: Several previous studies have examined the effect of CYP2D6 gene polymorphism on the efficacy and metabolism of tamoxifen (Tamoxifen Teva, Nolvadex) in the treatment of breast cancer. In the present study, the metabolic profiles associated with various CYP2D6 genotypes were evaluated. METHOD: In the present study 92 Turkish breast cancer patients with early-stage hormone receptor-positive tumors treated with adjuvant tamoxifen (20 mg) were evaluated for CYP2D6 genotype and metabolic profiles. Known side effects of tamoxifen treatment, including endometrial thickening, changes in serum lipid levels and bone density, and hepatosteatosis, were evaluated according to the CYP2D6 polymorphism. RESULT: The distribution of metabolic characteristics in the Turkish population was as follows: 77.1% normal metabolism, 11.5% intermediate metabolism, 5.2% ultrarapid metabolism, and 2.1% poor metabolism. The CYP2D6 genotypes associated with rapid metabolism were CYP2D6 3X*1/*1 duplication (DUP) and CYP2D6 2X*1/*2, while poor metabolism was associated with the genotypes CYP2D6 *3/*4 and CYP2D6 *6/*6. There was no statistically significant relationship between metabolic characteristics and bone density or hepatosteatosis. A statistically significant difference in total cholesterol and triglycerides was detected in lipid profile analysis (p = 0.003, p = 0.02). Assessment of endometrial thickness revealed a significant association of hyperplasia and poor metabolism, and an association between atrophy and ultrarapid metabolism (p = 0.01). CONCLUSION: Significant development of endometrial hyperplasia was identified among individuals with poor tamoxifen metabolism. As a result, tamoxifen may be a significant predictor of endometrial thickening among individuals with poor metabolic characteristics.

A unique case of merkel cell carcinoma with ovarian metastasis.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare cutaneous/mucosal malignancy with very aggressive biology and increasing incidence. Ovarian metastasis is an exceptionally rare site for MCC, and only two cases have been reported in the literature. CASE REPORT: We report MCC with ovarian metastasis. A 34 year-old female with previously excised MCC from preauricular skin presented with a pelvic mass 15 months after first diagnosis. Anti-cytokeratin (CK) 20 positivity, LCA (leucocyte common antigen), and TTF-1 (Thyroid transcription factor-1) negativity confirmed metastatic ovarian MCC. There was no evidence of recurrence or metastasis at 12 months after salpingooopherectomy. CONCLUSION: MCC should be considered in the differential diagnosis of primary and metastatic undifferentiated small round cell tumors of the ovary.

The Comparison of Patient-Controlled Remifentanil Administered by Two Different Protocols (Bolus and Bolus+Infusion) and Intramuscular Meperidine for Labor Analgesia.

OBJECTIVE: Nowadays, there are many pain relief methods for reducing the pain and stress of labor and delivery. In our study, two different remifentanil protocols (bolus and bolus+infusion) administered by patient-controlled analgesia method were compared with intramuscular meperidine for labor analgesia. METHODS: Ninety parturients who were scheduled for vaginal delivery were included in this study. Patients were randomly divided into 3 groups, with 15 primiparous and 15 multiparous patients in each group. Whenever a patient requested analgesics during the labor, Group M was given 1 mg kg(-1) intramuscular meperidine, Group B was given intravenous bolus patient-controlled remifentanil, and Group IB was given intravenous bolus+infusion patient-controlled remifentanil. Patients' systolic and diastolic blood pressure, heart rate, pain-comfort and sedation scores, remifentanil consumption, side effects, and Apgar scores of the newborns were evaluated during the labor and delivery. RESULTS: Patients' mean pain and comfort scores were significantly lower in Groups B and IB than in Group M at all time intervals except the first minute. Compared with Group IB, mean pain and comfort scores at 15, 30, 60, and 120 minutes were significantly higher in Group B. The mean sedation scores were similar among the groups. Total remifentanil consumption was lower in Group IB than in Group B, but it was not statistically significant. CONCLUSION: Patient-controlled intravenous bolus or bolus+infusion remifentanil provided more effective analgesia and patient comfort than intramuscular meperidine for labor analgesia. Especially during labor, bolus+infusion remifentanil administration provided better pain and patient comfort scores than bolus alone, without increasing remifentanil consumption.

Prenatal determination of the upper lesion level of spina bifida with three-dimensional ultrasound.

INTRODUCTION: To evaluate the role of three-dimensional (3D) sonography in the prenatal detection of the upper pole in fetuses with spina bifida. MATERIAL AND METHODS: Women admitted to a tertiary center with pregnancies with isolated open spina bifida were enrolled in the study. All fetuses had 3D sonography to predict the lesion level. The exact lesion level was ascertained using radiography and/or autopsy following the delivery at term or abortion. RESULTS: Forty-eight cases were eligible for this study. Twenty-eight fetuses were diagnosed in the second trimester and the lesion level was precisely predicted in 24 (86%) of them. In 14 (70%) of the 20 fetuses diagnosed in the last trimester, the level was accurately determined. The remaining 10 fetuses, from both the second and third trimesters, were found to have a lesion level that was within one segment of the predicted lesion level. The correct matching rate was 38/48 (79%), and agreement within one segment was achieved in all cases. DISCUSSION: According to our data, 3D ultrasound is useful for the prenatal determination of lesion level in spina bifida, which is an important prognostic factor.

Adenosine deaminase activity in patients with ovarian neoplasms.

PURPOSE: The aim of this study was to investigate the serum and peritoneal fluid adenosine deaminase (ADA) activity in patients with benign and malignant ovarian neoplasms. METHODS: This is a prospective cross-sectional study performed in Cukurova University, Department of Gynecologic Oncology. Eighty-four patients with ovarian mass were included in this study within 13 months. The levels of serum and peritoneal fluid ADA levels were measured and compared in patients with benign and malignant ovarian neoplasms and also low- and high-grade malignant tumors. RESULTS: Serum and peritoneal fluid ADA levels were found to be significantly higher in patients with ovarian cancers as compared with benign ovarian tumors (p = 0.001). Additionally, ADA levels were found to be significantly different according to the histopathological subtypes and grade of ovarian cancers. However, there was no significant difference for ADA levels between the benign and low-grade malignant tumors. There was an important correlation between the peritoneal fluid and serum ADA levels. CONCLUSIONS: Serum and peritoneal fluid ADA levels were found to be higher in malignant ovarian neoplasms. This finding may be useful to understand the biochemically characteristics of malignant ovarian tumors and ADA may be a useful biomarker in diagnosis and management of ovarian tumors.

Osseous metaplasia of the endometrium.

Osseous metaplasia of the endometrium is very rare finding, and usually these cases presented with secondary infertility. Other symptoms are pelvic pain, dyspareunia, menstrual irregularities, vaginal discharge and the passage of bony fragments in menstrual blood. Suspicious lesion could see by hysterosalpingography or by ultrasonography; however, conclusive diagnosis and treatment tool is hysteroscopy. The aetiology is unknown, but theories include retained fetal bone and osseous metaplasia of endometrial tissue. We present a patient with osseous metaplasia who had treated with hysteroscopy.